Wearable Device–Based Intervention for Promoting Patient Physical Activity After Lung Cancer Surgery

Key Points Question Is a wearable-based intervention effective for improving physical activity, cardiopulmonary function, and patient-reported outcomes after lung cancer surgery? Findings In this nonrandomized clinical trial with 74 intervention patients and 120 control patients, the intervention group had a smaller decrease in number of daily steps and time spent on moderate-to-vigorous physical activity (MVPA) at 2 weeks after surgery and a larger increase in daily steps and MVPA at 6 months after surgery. Meaning The wearable device intervention used in this trial improved physical activity and patient-reported dyspnea at 6 months after surgery, and these findings may guide the development of comprehensive rehabilitation programs that integrate wearable devices.


Background
Lung cancer is the most prevalent cancer, accounting for 11.6% of all cancer cases and 18.4% of all cancer-related deaths.The number of patients with lung cancer continues to rise.[1] Approximately 85% of primary lung cancers are non-small cell lung cancer (NSCLC), and surgical resection is considered the standard of care, offering the best chance of a cure.[2] However, only 14% of patients with NSCLC undergo surgical intervention.This population is increasingly experiencing long-term survival issues, [3] and the risk of disability associated with this procedure has gained prominence as a crucial patient-focused outcome.[4] Lung cancer surgery causes further deterioration of the quality of life (QoL), especially in the first 3-6 months after surgery.[5] For many patients, the risk of impaired QoL after surgery is an important consideration when deciding whether to proceed with the procedure.After surgical resection of lung cancer, reduced QoL may explain the functional limitations, decreased exercise capacity, alterations in pulmonary mechanics, [6] and leg muscle weakness observed in patients.[7] Physical activity (PA) can potentially improve physical function, including cardiorespiratory and muscle function, as well as QoL in patients with cancer.[8] However, many perioperative patients with lung cancer show reduced PA levels.Improving PA and fitness can help alleviate the physical and emotional symptoms experienced during cancer treatment, including surgery.[9] A decrease in PA following surgery can be attributed to many factors such as pain, drowsiness, surgical attachments, reduced quadriceps strength, [10] ventilatory impairment, [11] and dyspnea, [12] all contributing to decreased exercise tolerance.
Unfortunately, few strategies are currently available to enable immediate postoperative recovery and long-term functioning in patients undergoing lung cancer surgery.The effectiveness of multimodal intervention programs for these patients has not yet been adequately researched.Therefore, the aim of this study is to develop a comprehensive perioperative intervention program for patients undergoing lung cancer surgery.

Objectives
The aim of this study is to evaluate the development and efficacy of a comprehensive perioperative intervention program to improve postoperative PA in patients with lung cancer.We hypothesized that the perioperative comprehensive intervention program would improve cardiopulmonary function and QoL compared with the historical control group.The primary outcome is the change in the cardiorespiratory function (6-minute walk test [6MWT]) 6 months after surgery compared with baseline and historical control groups.Secondary outcomes are PA, QoL, fatigue and symptoms at baseline and 2 weeks and 6 months after surgery.

Study design
This is a single center, single-arm study with historical controls of patients undergoing pulmonary resection for NSCLC.The results of the intervention group are compared with those of a historical control group.The recruitment of participants is initiated at least one week prior to surgery.The intervention is carried out continuously from baseline (at the time of recruitment) until six months after surgery.

Exclusion criteria
1) Patients with multiple primary cancer, metastatic lung cancer, recurrent lung cancer, or history of other cancer in the last 3 years; 2) Patients who have received neoadjuvant chemotherapy and/or radiotherapy; 3) Patients who have not been measured at baseline because of changes in surgery schedule, treatment plan, or withdrawal of consent; 4) Patients who are confirmed as not pathologically NSCLC or metastatic after surgery; 5) Patients with limited physical capacity to participate in this intervention, including those with cardiac failure (New York Heart Association functional classes III and IV)), cerebrovascular disease (cerebral hemorrhage, cerebral infarction, transient ischemic attack, stroke, cerebrovascular accident), gait disability such as osteoarthritis (arthritis, osteoporosis, joint pain, rheumatoid arthritis), and kidney disease (chronic kidney failure).

Drop-out criteria
1) Need to receive adjuvant chemotherapy and/or radiotherapy; 2) Withdrawal of consent; 3) Researcher's discretion that it is difficult to continue this trial.

Sample size determination
Given that we had co-primary endpoints, our sample size calculation was based on the primary endpoint that necessitated the larger sample size of the two.In this study, we aimed to compare 6-minute walking distance (6MWD) and physical activity at 6 months after surgery between the intervention and control groups, with a mean effect size (Cohen d = 0.5) of α = 0.05 and 90% power.To achieve this, we needed 85 participants per group.Allowing for 20% loss to follow-up, we needed 100 participants per group.-Phase II: Immediate postoperative intervention (from discharge to 2 months after surgery).

Intervention
-Phase III: Postoperative intervention (from 2 months until six months after surgery).
*Outcomes are assessed at baseline (before surgery) and at 1 and 6 months after surgery.3. Symptoms: Check using pain scale (numeric rating scales), dyspnea, depression

Component of comprehensive intervention program
In the intervention group, the exercise component consists of 30 min of general education on exercise at baseline.At the beginning of the study, we perform a pre-exercise assessment with the CPET to determine the optimal individual exercise dose and identify cardiopulmonary limitations and contraindications.In this web-based approach, the CPET is mandatory to prescribe appropriate exercise and protect participants from overload.
Goal resetting and progression occur when participants complete the goal of the previous week (>70%).Participants receive the WAT, including real-time feedback, a heart rate monitor (to monitor compliance), and a logbook to report the frequency of exercises completed and record all activities (Fig. 4).

1) Preoperative period (phase 1)
During the preoperative intervention period, all participants receive a one-time personal training session that includes instructions on how to perform aerobic exercise (type, intensity, time and frequency), breathing muscle exercises and the use of the wearable device (Versa, Fitbit, USA).Participants receive printed education materials previously developed "Guidebook for healthy life after lung cancer surgery."The exercise regimen is as follows.
Patients receive standard postoperative care, including respiratory muscle training and ambulation, in the ward.We recommend ten repetitions with the incentive spirometer three times daily and at least 30 min of ward ambulation three times daily.
Upon discharge, the 6 MWT is conducted on patients in the intervention group to assess their condition and ensure the safety of the exercise regimen.During the 6 MWT, we monitor oxygen saturation and heart rate (HR).The results, including 6 MWD, maximal HR (HRmax), and minimal oxygen saturation, are recorded and used to tailor the exercise plan.We aim to set the target HRmax during phase 2 to not exceed the HRmax recorded during the 6 MWT.Patients with a history of cardiac problems or those who have experienced postoperative cardiovascular complications undergo continuous EKG monitoring during 6WMT; if there are any indications of cardiac distress or discomfort, a formal consultation with a cardiologist is initiated.Additionally, patients in the intervention group will receive an extra 30 min of education based on their 6 MWT before being discharged.
Until two months postoperative period.
From discharge until one month postoperatively, we recommend engaging in light walking and bedside activities not exceeding 4 METs and maintaining a maximum HR lower than the HRmax recorded during the 6 MWT.Additionally, patients should not exceed an increase of more than 3000 steps beyond the step count recorded on the day before discharge.The exercise regimen is as follows.

3) Late postoperative period (phase 3)
In the first 2 to 6 months after the operation, the program is adapted to the patients' conditions and the changes in their activities.If cardiovascular complications are observed or suspected immediately after the operation (procedure II), the patient is referred to the circulatory department for further clarification.Upon confirmation of no abnormalities, moderate to highintensity exercise is recommended as preoperative exercise.
If circulatory problems persist, goal adjustment is made based on steps and time in lowintensity exercise (steps per day), as in Intervention II.Unless specific circumstances exist, the standard exercise goal to enhance cardiopulmonary function is set at 30 min of moderateintensity exercise.The progress is monitored at 2-3 weeks intervals and goals are adjusted during telephone consultations.The increase in exercise duration is set at 10 minutes and can be increased, decreased, or maintained up to 30 minutes with patient consent.If a target is not met, the cause is investigated to increase PA.The exercise program is as follows.

Data analysis
We use an intention-to-treat approach for all analyses.The primary and co-primary outcomes were cardiopulmonary function and physical activity at 6 months after surgery, measured by the 6-minute walking distance (6MWD) and the number of daily steps.Physical activity was also measured with the time spent of MVPA as secondary outcome.Secondary outcomes were change in physical activity (number of daily steps and time spent of MVPA) at 2 weeks after surgery, physical activity (time spent of MVPA) at 6 months after surgery and changes in health related QOL including function and symptoms at 2 weeks and 6 months after surgery, using linear regression model.
Outcomes were compared using linear regression and a mixed model at each time point and change, respectively.For outcomes measured at 3 visits, we used linear mixed-effects models with the main effects of visits and visit group interaction terms to assess differences in outcomes when comparing the intervention and control groups.Random intercept effects were included to account for differences in outcomes between study participants at baseline.Statistical significance is set at P-value <0.05 as statistically significant.All analyses are performed using STATA version 16 (StataCorp LP, College Station, TX, USA).

Ethical considerations 9.1 Protection of participants
This study is conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practice (GCP) and the applicable regulatory requirement(s).

Informed consent
All participants and their legally acceptable representatives are informed of the purpose of the study.
We state that this study is conducted only for participants who have voluntarily confirmed their willingness to participate, and that they may refuse to participate in or withdraw from the study at any time without penalty or loss of benefits to which they are otherwise entitled.We also explain that signing the written informed consent form and participating in this study does not constitute a waiver of any of the participant's legal rights.
Informed consent is obtained on written, signed and dated forms.A copy of the signed informed consent form is given to participants and the original signed informed consent form is retained by the investigator.

Approval of Institutional Review Board
This study is approved by the Institutional Review Board (IRB) of Samsung Medical Center in Seoul, Korea (IRB no.SMC2015-11-025) to protect the rights, safety, and well-being of the participants.

Registration of clinical trial
Clinical Trials.govID: NCT03215537

Confidentiality
The records identifying the participants are kept confidential and, to the extent permitted by the applicable laws and/or regulations, they are not made publicly available.The confidentiality of the participant's information is assured and participant's identity is not disclosed to the public.This information is only used for statistical analysis for the purposes of this study.If the study results are published, the participants' identities remain confidential.
Participant identification records are coded with a unique identification number assigned by the examiner to protect their confidentiality.
During the collection, processing and storage of the information in the study, we use a security system to prevent unauthorized access to the data.

Figure 3 . 2 .
Figure 3. Intervention duration and timing of outcome assessments

Figure 5 .
Figure 5. Goal adjustment and management cycle

Figure 6 .
Figure 6.Algorithm for goal adjustment

-Figure 4 . 2 )
Figure 4. Example of aerobic exercise and muscle strength

4 )Factor-○
) -Time: MVPA ≥30 min -Type: walking, climb, stair climbing (if need, weight-bearing exercise) -Goal achievement: time achieve day /5 days -Initial setting: set up the initial goal based on patient baseline PA -Progression: biweekly -Goal increase (70%): increase MVPA 10-30 min (≤90 min/day) -Goal achievement (30%-70%): maintain -Goal fail (30%): decrease MVPA 10-30 min (≥30 min/day) -Counseling: 1) In hospital education at discharge, 2) Tele counseling, 3) Face to face -Monitoring: Continuous monitoring using WAT Example of endurance exercise and muscle strength Management for barriers by category Table 4. Example of barrier management by category Nutritional management for wound recovery after surgery and maintenance of appropriate weight -Nutritional counseling to control body fat and maintain muscle mass related to decreased cardiorespiratory function -Dietary training to overcome loss of appetite -Simple recipe training according to individual circumstances (e.g., seniors living alone) Primary outcome and co-primary outcome 1) Cardiopulmonary function 6 months post-operation: 6-min walking distance (m) 2) Physical activity 6 months post-operation: the number of daily steps ○ Secondary outcome 1) Physical fitness 2 weeks and 6 months post-operation: 6-min walking distance (m), grip strength (kg), and 30-s chair stand 2) Change in the level and intensity of PA at postoperative 2 weeks and 6 months 3) Pulmonary function 2 weeks and 6 months post-operation: FEV 1 , FVC, FEV 1 /FVC, and DLco 4) The score and each change of symptoms and QoL 2 weeks and 6 months post-operation: dyspnea, pain, fatigue, depression, and QoL 5) Incidence of post-operation complications This work is supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) [Nos.2015R1C1A2A01055805 and 2017R1A2B2006435].

Table 1 .
Component of the endurance exercise program by intervention phase

Table 2 .
Progression of goal adjustment by intervention phase

Table 3 .
Counseling and monitoring by intervention phase